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Progess in mechanism of nicotinic acid mediated by nicotinic acid receptor GPR109A

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Author:: No author available

Journal Title:: Chinese Journal of Pharmacology and Toxicology

Issue:: 1

DOI:: 10.3867/j.issn.1000-3002.2012.01.021

Key Word:: 动脉粥样硬化;烟酸受体;潮红;G蛋白偶联受体

Abstract：烟酸作为调脂药物应用于临床已经50多年,相对高剂量的烟酸具有广泛的调脂作用.越来越多的证据表明,烟酸单用或联合降低低密度脂蛋白胆固醇( LDL-C)药物使用能够延缓动脉粥样硬化(AS)的进程和降低发生心血管事件的风险；但它的作用机制一直不是很明确.2003年,三个研究小组同时发现了烟酸受体,使人们对烟酸的作用机制有了进一步认识.烟酸受体GPR109A是一种Gi蛋白偶联受体,主要表达于白色、棕色脂肪组织、脾和免疫细胞.研究表明,烟酸受体主要介导以下作用:①烟酸作用于脂肪细胞的烟酸受体,抑制脂肪组织甘油三酯(TG)的水解,降低血浆游离脂肪酸( FFA)；②烟酸作用于皮肤角质细胞和朗格汉细胞的烟酸受体诱导前列腺素分泌,引起皮肤血管舒张,引发潮红；③激活烟酸受体还可增加脂联素分泌,诱导中性粒细胞凋亡,上调过氧化物酶体增殖激活受体γ表达.

Reference

[1]Rakesh S, Birjmohun,Barbara A, Hutten,John J P, Kastelein,etc.Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials.[J].2005,45(2).
[2]Tunaru S,Pfeffer K,Offermanns S,etc.PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect.[J].2003,9(3).
[3]Nissen SE,Bachinsky WB,Lasala GP,etc.Effect of torcetrapib on the progression of coronary atherosclerosis.[J].2007,356(13).
[4]L A, CARLSON,L, ORO.The effect of nicotinic acid on the plasma free fatty acid; demonstration of a metabolic type of sympathicolysis.[J].1962,172.
[5]Kostylina G,Yousefi S,Simon D,etc.Neutrophil apoptosis mediated by nicotinic acid receptors (GPR109A).[J].2008,15(1).
[6]Christian Zellner,Clive R. Pullinger,Bradley E. Aouizerat,etc.Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors[J].2005,25(1).
[7]Gaidarov I,Maciejewski-Lenoir D,Hakak Y,etc.Langerhans cells release prostaglandin D2 in response to nicotinic acid.[J].2006,126(12).
[8]Gottesdiener K,De-Lepeleire I,Crumley TM,etc.Suppression of niacin-induced vasodilation with an antagonist to prostaglandin D2 receptor subtype 1.[J].2007,81(6).
[9]Hanson J,Gille A,Zwykiel S,etc.Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice.[J].2010,120(8).
[10]Knowles HJ,Te Poole R,Workman P,etc.Niacin induces PPARgamma expression and transcriptional activation in macrophages via HM74 and HM74a-mediated induction of prostaglandin synthesis pathways.[J].2006,71(5).
[11]Lai, E.,Waters, M. G.,Tata, J. R.,etc.Effects of a niacin receptor partial agonist, MK-0354, on plasma free fatty acids, lipids, and cutaneous flushing in humans[J].2008,2(5).
[12]Benyo Z,Gille A,Kero J,etc.GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing.[J].2005,115(12).
[13]Rudolf Altschul,Abram Hoffer,J.D. Stephen.Influence of nicotinic acid on serum cholesterol in man[J].1955,54(2).
[14]L A, CARLSON.Studies on the effect of nicotinic acid on catecholamine stimulated lipolysis in adipose tissue in vitro.[J].1963,173.
[15]Elshourbagy N,Hassall DG,Barnes AA,etc.Molecular identification of high and low affinity receptors for nicotinic acid.[J].2003,278(11).
[16]Taggart AKP,Kero J,Gan XD,etc.(D)-beta-hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G[J].2005,280(29).
[17]Gille A,Bennett CL,Offermanns S,etc.Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells.[J].2006,70(6).
[18]Plaisance, Eric P.,Lukasova, Martina,Offermanns, Stefan,etc.Niacin stimulates adiponectin secretion through the GPR109A receptor.[J].2009,59(3).
[19]Offermanns S.The nicotinic acid receptor GPR109A (HM74A or PUMA-G) as a new therapeutic target.[J].2006,27(7).